Resting-State Network Analysis Reveals Altered Functional Brain Connectivity in Essential Tremor.

INTRODUCTION: Essential tremor (ET) comprises motor and non-motor related features, while the current neuro-pathogenetic basis is still insufficient to explain the etiologies of ET. While cerebellum associated circuits have been discovered, the large-scale cerebral network connectivity in ET remains unclear. This study aimed to characterize the ET in terms of functional connectivity as well as network. We hypothesized that the resting-state network within cerebrum could be altered in ET patients. METHODS: Resting-state functional MRI (fMRI) was used to evaluate the inter- and intra-network connectivity as well as the functional activity in ET and normal control. Correlation analysis was performed to explore the relationship between resting-state network metrics and tremor features. RESULTS: Comparison of inter-network connectivity indicated a decreased connectivity between default mode network and ventral attention network in ET group (P<0.05). Differences in functional activity (assessed by amplitude of low frequency fluctuation, ALFF) were found in several brain regions participating in various resting-state networks (P<0.05). ET group generally have higher degree centrality over normal control. Correlation analysis has revealed that tremor features are associated with inter-network connectivity (|r|=0.135-0.506), ALFF (|r|=0.313-0.766), and degree centrality (|r|=0.523-0.710). CONCLUSION: Alterations in the cerebral network of ET was detected by using resting-state fMRI, demonstrating a potentially useful approach to explore the cerebral alterations in ET.

Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Imbalance of synaptic and extrasynaptic NMDA receptors induced by the deletion of CRMP1 accelerates age-related cognitive decline in mice.

Collapsin response mediator protein 1 (CRMP1) is involved in semaphorin 3A signaling pathway, promoting neurite extension and growth cone collapse. It is highly expressed in the nervous system, especially the hippocampus. The crmp1 knockout (KO) mice display impaired spatial learning and memory, and this phenomenon seemingly tends to deteriorate with age. Here we investigated whether CRMP1 is involved in age-related cognitive decline in WT and crmp1 KO mice at adult, middle-aged and older stages. The results revealed that cognitive dysfunction in the Morris water maze task became more severe and decreased glutamate and glutamine level in middle-aged crmp1 KO mice. Additionally, increasing levels of extrasynaptic NMDA receptors and phosphorylation of Tau were observed in middle-aged crmp1 KO mice, leading to synaptic and neuronal loss in the CA3 regions of hippocampus. These findings suggest that deletion of CRMP1 accelerates age-related cognitive decline by disrupting the balance between synaptic and extrasynaptic NMDA receptors, resulting in the loss of synapses and neurons.

Joint diffusional kurtosis magnetic resonance imaging analysis of white matter and the thalamus to identify subcortical ischemic vascular disease.

Identifying subcortical ischemic vascular disease (SIVD) in older adults is important but challenging. Growing evidence suggests that diffusional kurtosis imaging (DKI) can detect SIVD-relevant microstructural pathology, and a systematic assessment of the discriminant power of DKI metrics in various brain tissue microstructures is urgently needed. Therefore, the current study aimed to explore the value of DKI and diffusion tensor imaging (DTI) metrics in detecting early-stage SIVD by combining multiple diffusion metrics, analysis strategies, and clinical-radiological constraints. This prospective study compared DKI with diffusivity and macroscopic imaging evaluations across the aging spectrum including SIVD, Alzheimer's disease (AD), and cognitively normal (NC) groups. Using a white matter atlas and segregated thalamus analysis with considerations of the pre-identified macroscopic pathology, the most effective diffusion metrics were selected and then examined using multiple clinical-radiological constraints in a two-group or three-group paradigm. A total of 122 participants (mean age, 74.6 ± 7.38 years, 72 women) including 42 with SIVD, 50 with AD, and 30 NC were evaluated. Fractional anisotropy, mean kurtosis, and radial kurtosis were critical metrics in detecting early-stage SIVD. The optimal selection of diffusion metrics showed 84.4-100% correct classification of the results in a three-group paradigm, with an area under the curve of .909-.987 in a two-group paradigm related to SIVD detection (all P < .001). We therefore concluded that greatly resilient to the effect of pre-identified macroscopic pathology, the combination of DKI/DTI metrics showed preferable performance in identifying early-stage SIVD among adults across the aging spectrum.

Anesthetic modulation of water diffusion: Insights from a diffusion tensor imaging study.

Diffusion tensor imaging (DTI) in animal models are essential for translational neuroscience studies. A critical step in animal studies is the use of anesthetics. Understanding the influence of specific anesthesia regimes on DTI-derived parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), is imperative when comparing results between animal studies using different anesthetics. Here, the quantification of FA and MD under different anesthetic regimes, alpha-chloralose and isoflurane, is discussed. We also used a range of b-values to determine whether the anesthetic effect was b-value dependent. The first group of rats (n = 6) was anesthetized with alpha-chloralose (80 mg/kg), whereas the second group of rats (n = 7) was anesthetized with isoflurane (1.5%). DTI was performed with b-values of 500, 1500, and 1500s/mm2, and the MD and FA were assessed individually. Anesthesia-specific differences in MD were apparent, as manifested by the higher estimated MD under isoflurane anesthesia than that under alpha-chloralose anesthesia (P < 0.001). MD values increased with decreasing b-value in all regions studied, and the degree of increase when rats were anesthetized with isoflurane was more pronounced than that associated with alpha-chloralose (P < 0.05). FA quantitation was also influenced by anesthesia regimens to varying extents, depending on the brain regions and b-values. In conclusion, both scanning parameters and the anesthesia regimens significantly impacted the quantification of DTI indices.

Brain alterations in ovariohysterectomized rats revealed by diffusion tensor imaging.

OBJECTIVES: Women undergoing hysterectomy with oophorectomy have an increased risk of Alzheimer's disease and Parkinson's disease. However, postoperative neuroimaging data on pathogenic processes in the brain are limited. The aim of this study was to investigate the potential effect of ovariohysterectomy on brain integrity in rat model using diffusion tensor imaging (DTI) technique for the first time. METHODS: We enrolled 13 rats each in the control and ovariohysterectomy groups. Rats in the ovariohysterectomy group underwent the ovariohysterectomy at 7 weeks of age, and all rats underwent DTI scans at 9 weeks of age. The DTI-derived parameters, such as fractional anisotropy and mean diffusivity, were compared between the control and ovariohysterectomy groups. RESULTS: Compared to the control group, the ovariohysterectomy group showed significantly lower fractional anisotropy in various brain regions, including the corpus callosum, bilateral striatum, and bilateral cortex (all P  < 0.05), suggesting neuronal injury in ovariohysterectomized rats. Mean diffusivity did not differ significantly between groups (all P  > 0.05). CONCLUSION: Rats undergoing ovariohysterectomy had lower fractional anisotropy compared to control in widespread brain regions, suggesting neuronal injury and demyelination. Therefore, neuroimaging should be performed to monitor brain alterations in women after hysterectomy with bilateral oophorectomy in clinical settings.

Reproducibility of diffusion tensor imaging-derived parameters: implications for the streptozotocin-induced type 1 diabetic rats.

OBJECTIVE: Diffusion tensor imaging (DTI) is a useful approach for studying neuronal integrity in animals. However, the test-retest reproducibility of DTI techniques in animals has not been discussed. Therefore, the first part of this work was to systematically elucidate the reliability of DTI-derived parameters in an animal study. Subsequently, we applied the DTI approach to an animal model of diabetes in a longitudinal manner. MATERIALS AND METHODS: In Study 1, nine rats underwent two DTI sessions using the same scanner and protocols, with a gap of 4 weeks. The reliability of the DTI-derived parameters was evaluated in terms of sessions and raters. In Study 2, nine rats received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to develop diabetes. Longitudinal DTI scans were used to assess brain alterations before and 4 weeks after STZ administration. RESULTS: In the test-retest evaluation, the inter-scan coefficient of variation (CoV) ranged from 3.04 to 3.73% and 2.12-2.59% for fractional anisotropy (FA) and mean diffusivity (MD), respectively, in different brain regions, suggesting excellent reproducibility. Moreover, rater-dependence had minimal effects on FA and MD quantification, with all inter-rater CoV values less than 4%. Following the onset of diabetes, FA in striatum and cortex were noted to be significantly lower relative to the period where they had not developed diabetes (both P < 0.05). However, when compared to the control group, a significant change in FA caused by diabetes was detected only in the striatum (P < 0.05), but not in the cortex. CONCLUSION: These results demonstrate good inter-rater and inter-scan reliability of DTI in animal studies, and the longitudinal setting has a beneficial effect on detecting small changes in the brain due to diseases.

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control.

Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s-/-) mouse. The Blm-s-/- mice breed normally and exhibit grossly normal development. However, global depletion of Blm-s is highly associated with depression- and anxiety-related behaviors in adult mutant mice with intact learning and memory capacity. Functional magnetic resonance imaging of adult Blm-s-/- mice reveals reduced connectivity mainly in the ventral dentate gyrus (vDG) of the hippocampus with no alteration in the dorsal DG connectivity and in total hippocampal volume. At the cellular level, BLM-s is expressed in DG granule cells (GCs), and Blm-s-/- mice show reduced dendritic complexity and decreased spine density in mature GCs. Electrophysiology study uncovers that mature vGCs in adult Blm-s-/- DG are intrinsically more excitable. Interestingly, certain genetic variants of the human Blm homologue gene (VPS50) are significantly associated with depression traits from publicly resourced UK Biobank data. Taken together, BLM-s is required for the hippocampal mood control function. Loss of BLM-s causes abnormality in the electrophysiology and morphology of GCs and a disrupted vDG neural network, which could underlie Blm-s-null-associated anxiety and depression.

Differences in brain activity between normal and diabetic rats under isoflurane anesthesia: a resting-state functional MRI study.

BACKGROUND: Altered neural activity based on the fractional amplitude of low-frequency fluctuations (fALFF) has been reported in patients with diabetes. However, whether fALFF can differentiate healthy controls from diabetic animals under anesthesia remains unclear. The study aimed to elucidate the changes in fALFF in a rat model of diabetes under isoflurane anesthesia. METHODS: The first group of rats (n = 5) received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to cause the development of diabetes. The second group of rats (n = 7) received a single intraperitoneal injection of the same volume of solvent. Resting-state functional magnetic resonance imaging was used to assess brain activity at 4 weeks after STZ or solvent administration. RESULTS: Compared to the healthy control animals, rats with diabetes showed significantly decreased fALFF in various brain regions, including the cingulate cortex, somatosensory cortex, insula, and striatum (all P < 0.05). The decreased fALFF suggests the aberrant neural activities in the diabetic rats. No regions were detected in which the control group had a lower fALFF than that in the diabetes group. CONCLUSIONS: The results of this study demonstrated that the fALFF could be used to differentiate healthy controls from diabetic animals, providing meaningful information regarding the neurological pathophysiology of diabetes in animal models.

Prospective Memory and Default Mode Network Functional Connectivity in Normal and Pathological Aging.

BACKGROUND: Prospective memory (PM), the ability to execute a previously formed intention given the proper circumstance, has been proven to be vulnerable to Alzheimer's disease. Previous studies have indicated the involvement of the frontoparietal networks; however, it is proposed that PM may also be associated with other neural substrates that support stimulus-dependent spontaneous cognition. OBJECTIVE: The present study aimed to examine the hypothesis that PM deficit in Alzheimer's disease is related to altered functional connectivity (FC) within the default mode network (DMN). METHODS: Thirty-four patients with very mild or mild dementia (17 with Alzheimer's disease and 17 with subcortical ischemic vascular disease) and 22 cognitively-normal participants aged above 60 received a computerized PM task and resting-state functional magnetic resonance imaging study. Seed-based functional connectivity analysis was performed at group level within the DMN. RESULTS: We found that the dementia groups showed worse PM performance and altered FC within the DMN as compared to the normal aging individuals. The FC between the medial prefrontal cortices and precuneus/posterior cingulate cortex was significantly correlated with PM in normal aging, while the FC between the right precuneus and bilateral inferior parietal lobules was correlated with PM in patients with Alzheimer's disease. CONCLUSION: These findings support a potential role for the DMN in PM, and corroborate that PM deficit in Alzheimer's disease was associated with altered FC within the posterior hubs of the DMN, with spatial patterning different from normal aging.

Carbon fibre-supported hierarchical NiCo layered double hydroxide nanosheets as non-enzymatic glucose sensors for sport drinks and serum.

We report a systematic study of carbon fibre (CF)-supported NiCo layered double hydroxide nanosheets (LDHNs) with and without heat treatment at 200 and 400 °C (CF-NiCo LDHN200 and CF-NiCo oxide nanoparticles (NPs), respectively) as catalysts and sensors for glucose oxidation reactions (GORs). Tafel measurements for the GORs showed that the exchange current density of CF-NiCo LDHN was 1.91 × 10-3 mA·cm-2 at an early rest potential of -0.422 V. This was markedly higher than those of CF-NiCo LDHN200 (1.22 × 10-3 mA·cm-2 at - 0.352 V) and CF-NiCo oxide NP (1.18 × 10-3 mA·cm-2 at -0.327 V). The electron transfer number and Tafel slopes suggested that the glucose dehydrogenation step and one-electron release occurred first in the GORs. Amperometric measurements revealed high recoveries (101.92% and 98.92%) and low relative standard deviations (1.98% and 2.34%) for the determination of glucose using the CF-NiCo LDHN in sports drink samples and human serum.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Discriminating subcortical ischemic vascular disease and Alzheimer's disease by diffusion kurtosis imaging in segregated thalamic regions.

Differentiating between subcortical ischemic vascular disease (SIVD), Alzheimer's disease (AD), and normal cognition (NC) remains a challenge, and reliable neuroimaging biomarkers are needed. The current study, therefore, investigated the discriminative ability of diffusion kurtosis imaging (DKI) metrics in segregated thalamic regions and compare with diffusion tensor imaging (DTI) metrics. Twenty-three SIVD patients, 30 AD patients, and 24 NC participants underwent brain magnetic resonance imaging. The DKI metrics including mean kurtosis (MK), axial kurtosis (Kaxial ) and radial kurtosis (Kradial ) and the DTI metrics including diffusivity and fractional anisotropy (FA) were measured within the whole thalamus and segregated thalamic subregions. Strategic correlations by group, thalamo-frontal connectivity, and canonical discriminant analysis (CDA) were used to demonstrate the discriminative ability of DKI for SIVD, AD, and NC. Whole and segregated thalamus analysis suggested that DKI metrics are less affected by white matter hyperintensities compared to DTI metrics. Segregated thalamic analysis showed that MK and Kradial were notably different between SIVD and AD/NC. The correlation analysis between Kaxial and MK showed a nonsignificant relationship in SIVD group, a trend of negative relationship in AD group, and a significant positive relationship in NC group. A wider spatial distribution of thalamo-frontal connectivity differences across groups was shown by MK compared to FA. CDA showed a discriminant power of 97.4% correct classification using all DKI metrics. Our findings support that DKI metrics could be more sensitive than DTI metrics to reflect microstructural changes within the gray matter, hence providing complementary information for currently outlined pathogenesis of SIVD and AD.

Dissociable Functional Brain Networks Associated With Apathy in Subcortical Ischemic Vascular Disease and Alzheimer's Disease.

Few studies have investigated differences in functional connectivity (FC) between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD), especially in relation to apathy. Therefore, the aim of this study was to compare apathy-related FC changes among patients with SIVD, AD, and cognitively normal subjects. The SIVD group had the highest level of apathy as measured using the Apathy Evaluation Scale-clinician version (AES). Dementia staging, volume of white matter hyperintensities (WMH), and the Beck Depression Inventory were the most significant clinical predictors for apathy. Group-wise comparisons revealed that the SIVD patients had the worst level of "Initiation" by factor analysis of the AES. FCs from four resting state networks (RSNs) were compared, and the connectograms at the level of intra- and inter-RSNs revealed dissociable FC changes, shared FC in the dorsal attention network, and distinct FC in the salient network across SIVD and AD. Neuronal correlates for "Initiation" deficits that underlie apathy were explored through a regional-specific approach, which showed that the right inferior frontal gyrus, left middle frontal gyrus, and left anterior insula were the critical hubs. These findings broaden the disconnection theory by considering the effect of FC interactions across multiple RSNs on apathy formation.

Development, integration and use of an ultra-high-strength gradient system on a human-size 3 T magnet for small animal MRI.

This study aims to integrate an ultra-high-strength gradient coil system on a clinical 3 T magnet and demonstrate its preclinical imaging capabilities. Dedicated phantoms were used to qualitatively and quantitatively assess the performance of the gradient system. Advanced MR imaging sequences, including diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM), were implemented and executed on an ex vivo specimen as well as in vivo rats. The DTI and QSM results on the phantom agreed well with those in the literature. Furthermore, studies on ex vivo specimens have demonstrated the applicability of DTI and QSM on our system to probe microstructural changes in a mild traumatic brain injury rat model. The feasibility of in vivo rat DTI was also demonstrated. We showed that the inserted ultra-high-strength gradient coil was successfully integrated on a clinically used magnet. After careful tuning and calibration, we verified the accuracy and quantitative preclinical imaging capability of the integrated system in phantom and in vivo rat brain experiments. This study can be essential to establish dedicated animal MRI platform on clinical MRI scanners and facilitate translational studies at clinical settings.

Design and Implementation of a Transmit/Receive Ultrasound Phased Array for Brain Applications.

Focused ultrasound phased array systems have attracted increased attention for brain therapy applications. However, such systems currently lack a direct and real-time method to intraoperatively monitor ultrasound pressure distribution for securing treatment. This study proposes a dual-mode ultrasound phased array system design to support transmit/receive operations for concurrent ultrasound exposure and backscattered focal beam reconstruction through a spherically focused ultrasound array. A 256-channel ultrasound transmission system was used to transmit focused ultrasonic energy (full 256 channels), with an extended implementation of multiple-channel receiving function (up to 64 channels) using the same 256-channel ultrasound array. A coherent backscatter-received beam formation algorithm was implemented to map the point spread function (PSF) and focal beam distribution under a free-field/transcranial environment setup, with the backscattering generated from a strong scatterer (a point reflector or a microbubble-perfused tube) or a weakly scattered tissue-mimicking graphite phantom. Our results showed that PSF and focal beam can be successfully reconstructed and visualized in free-field conditions and can also be transcranially reconstructed following skull-induced aberration correction. In vivo experiments were conducted to demonstrate its capability to preoperatively and semiquantitatively map a focal beam to guide blood-brain barrier opening. The proposed system may have potential for real-time guidance of ultrasound brain intervention, and may facilitate the design of a dual-mode ultrasound phased array for brain therapeutic applications.

Ultrasonic Nakagami Imaging of High-intensity Focused Ultrasound-induced Thermal Lesions in Porcine Livers: Ex Vivo Study.

High-intensity focused ultrasound (HIFU) has demonstrated the capacity to be used for local thermal ablation in clinical surgery; however, relying solely on conventional ultrasound B-mode imaging to monitor HIFU thermal ablation and determine ablation levels remains a challenge. Here, we experimentally demonstrate the ability to use Nakagami imaging to monitor HIFU-induced thermal lesions in porcine livers ex vivo. Ultrasonic Nakagami imaging has been proven to be able to characterize tissues with different scatterer concentrations and distributions. The pathological sections from HIFU thermally ablated porcine liver tissues reveal that normal and denatured tissues significantly differ in scatterer concentration and distribution. Therefore, we believe that Nakagami imaging can be used to monitor thermal ablation by tracing Nakagami parameter changes in liver tissues. The ex vivo porcine liver experiments were performed using a homemade HIFU device synchronized with a commercial diagnostic ultrasound scanner to obtain the ultrasound envelope data before and after thermal ablation. These data were used to evaluate the performance of thermal lesion characterization using Nakagami imaging and were compared with those derived from conventional B-mode imaging. Experimental results showed that Nakagami imaging can be used to identify thermal lesions, which are difficult to visualize using conventional B-mode imaging because there is no apparent bubble formation. In cases with apparent bubble formation, Nakagami imaging could provide a more accurate estimation of lesion size and position. In addition, the Nakagami imaging algorithm is characterized by low computational complexity, which means it can be easily integrated as postprocessing for existing array imaging systems.

Identification of plant vacuolar transporters mediating phosphate storage.

Plant vacuoles serve as the primary intracellular compartments for inorganic phosphate (Pi) storage. Passage of Pi across vacuolar membranes plays a critical role in buffering the cytoplasmic Pi level against fluctuations of external Pi and metabolic activities. Here we demonstrate that the SPX-MFS proteins, designated as PHOSPHATE TRANSPORTER 5 family (PHT5), also named Vacuolar Phosphate Transporter (VPT), function as vacuolar Pi transporters. Based on (31)P-magnetic resonance spectroscopy analysis, Arabidopsis pht5;1 loss-of-function mutants accumulate less Pi and exhibit a lower vacuolar-to-cytoplasmic Pi ratio than controls. Conversely, overexpression of PHT5 leads to massive Pi sequestration into vacuoles and altered regulation of Pi starvation-responsive genes. Furthermore, we show that heterologous expression of the rice homologue OsSPX-MFS1 mediates Pi influx to yeast vacuoles. Our findings show that a group of Pi transporters in vacuolar membranes regulate cytoplasmic Pi homeostasis and are required for fitness and plant growth.

Inter-Strain Differences in Default Mode Network: A Resting State fMRI Study on Spontaneously Hypertensive Rat and Wistar Kyoto Rat.

Genetic divergences among mammalian strains are presented phenotypically in various aspects of physical appearance such as body shape and facial features. Yet how genetic diversity is expressed in brain function still remains unclear. Functional connectivity has been shown to be a valuable approach in characterizing the relationship between brain functions and behaviors. Alterations in the brain default mode network (DMN) have been found in human neuropsychological disorders. In this study we selected the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (WKY), two inbred rat strains with close genetic origins, to investigate variations in the DMN. Our results showed that the major DMN differences are the activities in hippocampal area and caudate putamen region. This may be correlated to the hyperactive behavior of the SHR strain. Advanced animal model studies on variations in the DMN may have potential to shed new light on translational medicine, especially with regard to neuropsychological disorders.

Investigation of Readout RF Pulse Impact on the Chemical Exchange Saturation Transfer Spectrum.

Chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) is capable of both microenvironment and molecular imaging. The optimization of scanning parameters is important since the CEST effect is sensitive to factors such as saturation power and field homogeneity. The aim of this study was to determine if the CEST effect would be altered by changing the length of readout RF pulses. Both theoretical computer simulation and phantom experiments were performed to examine the influence of readout RF pulses. Our results showed that the length of readout RF pulses has unremarkable impact on the Z-spectrum and CEST effect in both computer simulation and phantom experiment. Moreover, we demonstrated that multiple refocusing RF pulses used in rapid acquisition with relaxation enhancement (RARE) sequence induced no obvious saturation transfer contrast. Therefore, readout RF pulse has negligible effect on CEST Z-spectrum and the optimization of readout RF pulse length can be disregarded in CEST imaging protocol.